This invention concerns a novel therapeutic treatment for male sexual impotence by the administration of "trazodone" which is the USAN-approved generic name for 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo [4,3-a]pyridin-3(2H)-one. Trazodone and related compounds are described in U.S. Pat. No. 3,381,009 as having tranquilizing and hypotensive activity. Trazodone has also been described as having utility in the treatment of individuals suffering from the acute phases of stroke (U.S. Pat. No. 4,154,832) and for use in the treatment of Parkinsonism (U.S. Pat. No. 4,162,318) and in combination with L-DOPA in treating Parkinsonism (U.S. Pat. No. 4,131,675). However, trazodone is best known as a potent and safe antidepressant agent and has been accepted internationally for use in the clinical treatment of depression.
Male impotence is a sexual dysfunction which relates to difficulty in achieving and maintaining penile erection. Currently, male impotence is a broad-ranging problem of social, psychologic, and medical significance. There exists today a diversity of possible causes of impotence as well as suggested methods of treatment. These have been described in a number of available literature reviews on male impotence and on male sexual dysfunctioning in general. While impotence can result from psychogenic or physical causes, a review by L. M. Martin in Geriatrics, (December 1980), pages 79-83; emphasizes that organic causes of impotence are more common than has been currently believed. Any condition that impairs the endocrine, vascular, neurologic, or anatomic systems can produce impotence. Among various causes of impotence that are specifically implicated are: diabetes, surgery, vascular disease, hypertension and hardening of arteries, side-effects from drugs, and hormonal imbalance.
Concerning the treatment of impotence, H. G. Kudish in Postgraduate Medicine, Vol. 74/4 (October 1983), pages 233-240; lists therapies for impotence as being in two categories: surgical and non-surgical. The surgical category comprises implantation of a penile prosthetic device; revascularization of the penis; and incision or excision of Peyronie's plaques. The non-surgical category comprises sex therapy, endocrine therapy, pharmacologic therapy, and electrostimulation. Non-surgical therapies, when effective, are the treatments of choice. Of these, the favored treatment in most instances would be pharmacologic therapy if it was effective. Unfortunately, the use of pharmacologic agents in treatment of impotence has achieved little success. This is evidenced by the absence of any recognized accepted pharmacologic treatment for use in male impotence, although anecdotal reports of the use of various agents, compositions, and formulations abound. Currently, yohimbine, a drug occasionally prescribed for hypertension, is being studied for possible use in the treatment of impotence. Improvement in erectile function after administration of the .alpha.-adrenergic blocking agent phenoxybenzamine has also been reported anecdotally.
While reports of beneficial drug effects on sexual functioning in the male are mainly anecdotal, a considerable literature deals with sexual dysfunction associated with drug treatment. In general, these effects are considered to be undesirable side effects from any of many medications including inter alia, antihypertensives and antidepressants. While most types of sexual dysfunction associated with drug administration appear to be medically benign and reversible with drug discontinuation, an important exception is priapism, which necessitates prompt urologic consultation and which in many cases may require surgical intervention. While not well understood, priapism, a prolonged painful and abnormal erection of the penis, can have numerous possible etiologies in addition to administration of pharmacologic agents. It is felt that priapism may involve a different physiologic mechanism than that for normal penile erection. In the state of priapism the viscosity of the blood engorging the penile tissue increases abnormally (of: The Merck Manual, 14th Edition (1982) page 1602). Although the onset of priapism can in some instances be initiated by sexual stimuli, the prolonged painful abnormal erection persists long after the sexual excitement is gone. One reason for the poor understanding of the underlying causes and mechanisms of development of priapism is the low frequency of occurrence of priapism. Since priapism frequently requires surgical intervention, impotence is a possible consequence.
Although several drugs have been reported in the literature as being associated with priapism (see for example: J. E. Mitchell and M. K. Popkin, "Antipsychotic Drug Therapy and Sexual Dysfunction in Man" in Am. J. Psychiatry, 139:5 (May 1982) pages 633-637); none of these drugs is employed in treating penile erectile dysfunction. In fact, the potential permanent impotence which can result from priapism causes any pharmacologic agent which may be causally related to priapism to be contra-indicated for use in males. It is to be recognized that induction of the abnormal penile erection of priapism would not be considered as a desirable treatment for male impotence. It should also be understood that known agents associated with priapism are not effective in the induction of useful erectile activity in impotent males.
Also found among the many drugs reported to be associated in cases of priapism is trazodone. Representative of these reports are the following:
(1) Anon., The Medical Letter, 20(658), Mar. 30, 1984, page 35. PA1 (2) Aronoff, The Lancet, Apr. 14, 1984, page 856. PA1 (3) Lansky, et al., J. Clin. Psychiatry, 45:232-233, 1984. PA1 (4) Scher, et al., Am. J. Psychiatry, 140:1362-1363, 1983. PA1 (5) Raskin, ibid., 142:1, 1985.
While the incidence of trazodone-associated priapism or undesired abnormal erectile activity is very low, nonetheless, these reports would act to teach away from the use of trazodone in treating male impotence, especially since other agents associated with priapism have not been found to be useful in this regard. As the study of the relationship of trazodone and erectile activity has proceeded, however, it has been discovered that trazodone unexpectedly can produce useful erectile activity in male mammals. This surprising finding has led to the instant unobvious invention.
In summary, trazodone and its pharmaceutically acceptable salts have heretofore been reported as having only unwanted abnormal and potentially harmful effects on erectil function of male patients. There exists nothing in the prior art which teaches or suggests that trazodone would be useful in the treatment of impotence in males with compromised penile erection function.